CRISPR-edited cells for cancer treatment appear safe

Results published from a pioneering clinical trial in the USA have confirmed for the first time that treatment with genome-edited cells appears safe.

The first clinical trial of its kind, three patients with advanced cancers were treated with genome-edited immune cells. The finding that these cells can be used to treat cancer patients opens new avenues of research in the field of gene therapy.

'The possibilities are limitless based on our imagination and scientific focus,' said Dr Edward Stadtmauer, from the University of Pennsylvania, Philadelphia, and co-leader of the trial. 'We hope this is the beginning of the next generation of engineering cells to help many different diseases and many different tumours.'

The study, published in the journal Science, follows on from previously reported early results (see Bionews 1023). The researchers took immune cells from cancer patients and engineered them outside of the body to better target cancer cells, using a harmless virus. Then, in a first for the field, the team also used CRISPR/Cas9 genome editing to remove three genes from the immune cells. One of the genes they removed was an 'off-switch', which cancers can flip to survive and escape the body's defences.

After six weeks, the cells were put back in the patients. Analysis of the cells months later demonstrated that the cells were still able to kill tumours. Previous data has shown that these cells normally lose function within days, 'the fact that the CRISPR-edited cells in this study retained anti-tumour function for a significantly longer period of time after a single infusion is very encouraging,' said Dr Carl June, Professor in Immunotherapy and director of the Centre for Cellular Immunotherapies in the Abramson Cancer Centre.

As an early clinical trial, the researchers were looking for whether the therapy was safe, rather than whether it was effective. Importantly, although some off-target effects in the cells' DNA were reported, these faded over time and did not cause harm to the patients. Overall, of the three patients tested, all tolerated the treatment well and none showed any serious adverse effects.  

Before now, researchers had been unsure whether genome editing could safely and precisely edit a cell's DNA, without causing serious side effects in patients. The finding that genome-edited cells appear safe has subsequently excited other experts in the field.

'The authors have set another milestone here by showing the feasibility of using CRISPR to edit human immune cells,' said Professor Waseem Qasim, Professor of Cell and Gene Therapy at University College London, who was not involved in the study. 'These gene-editing technologies are evolving rapidly, and we can expect to see more trials using similar approaches.'

The trial's leader, Dr June, has stated that the trial won't continue as the 2016 genome-editing technology they used is already outdated. Newer CRISPR-based approaches can inactivate genes without cutting DNA, which should reduce the cancer risk even further.

'The most important finding of the study is that these new engineered T cells don't seem to trigger an immune response against them, which in turn could have led to lots of side effects,' said Professor Justin Stebbing, Professor of Cancer Medicine and Medical Oncology at Imperial College London, who was not involved in the study.

A larger trial with more patients is needed to fully demonstrate the safety of this approach.